However, calculating your biological age is not so easy, and may not even be a well-defined problem. Not surprisingly there are many approaches, and there is no shortage of companies that have attempted to commercialize the undertaking while making unfounded claims. The two basic approaches are using physiological biomarkers (e.g. VO2max, cholesterol levels, balance, etc.), or using molecular biomarkers from DNA such as telomere length or DNA methylation.
In an article in the Wall Street Journal, the reporter tested several commercial kits that purport to measure biological age based on DNA methylation:
“How old am I, really? I spat in a tube, swabbed the inside of my cheek and pricked my finger to find out. I mailed my samples to three companies that promised to tell me my “biological age” based on chemical modifications of my DNA. The results, the companies said, would be based not on when I was born, but on how much my cells and organs had aged. The verdicts arrived by email a few weeks later: I was 33…or 41? The tests cost a few hundred dollars each.”
Methylated DNA is associated with bundling of the DNA into compact chromatin that prevents expression of genes. One of the most common forms of DNA methylation is attaching a methyl group (CH3) to the cytosine (C) base in a CpG dinucleotide (i.e cytosine followed by guanine nucleotide; p refers to phosphate group between two nucleotides). In general, high levels of CpG methylation in the promoter region of a gene can lead to gene silencing, meaning that the associated gene is less likely to be transcribed and its protein product produced. This can effectively turn off the gene's expression. During aging, researchers have found that promoters of certain genes become hypermethylated at CpG sites turning expression off, which may contribute to the aging process or be a side effect (Figure 1). Regardless, this hypermethylation can be detected and quantified as an aging biomarker.
More specifically, researchers have developed epigenetic clocks, which are mathematical models based on DNA methylation patterns at specific sites in the genome. DNA methylation is considered to be an epigenetic change because the DNA modifications can be passed on to progeny cells although the DNA sequence itself is not altered (i.e. genetic mutation). Various epigenetic clocks have been developed, such as the Horvath clock and the Hannum clock, which rely on different sets of CpG sites for age estimation. For example, the original Horvath clock used 353 CpG sites, but subsequent versions and refinements have included more sites for improved accuracy. The Hannum clock uses a set of 71 CpG sites from the DNA methylation data to estimate biological age. These specific sites were identified as highly correlated with age in blood samples.
What were the results from the WSJ reporter's experiment?
"I would have felt smug, but Novos also provided a more standard biological age estimate. I was 41, it concluded. Tally’s test put my biological age at 33. Elysium said it was closer to 34—but said my heart was a sprightly 32 while my liver and brain were 43. I celebrated my 36th birthday in May."
Of course the idea of measuring biological age is not to rediscover your chronological age, but to provide information on whether you are more or less healthy relative to the average person of your chronological age. The author also interviewed Matt Kaeberlein, a scientist running a lab investigating aging in various model organisms, and who was skeptical of the validity of these tests:
"Kaeberlein, who consults for Novos but said he doesn’t endorse their products, said he has tried DNA methylation tests that put his biological age in a range from 36 to 59. He is 52. “These tests are for entertainment value only,” he said."
As mentioned above, an alternative to the DNA methylation based methods is to assess a broad array of physiological markers that measure overall heath of the body. In a past post, I described an article in the Proceedings of the National Academy of Sciences (PNAS) that made a systematic attempt to quantify biological age, and the change in biological age over time. The authors explored 18 different biomarkers which included the following:
- Glycated hemoglobin level (HbA1C) (blood sugar)
- Cardiorespiratory Fitness (estimate of VO2 max)
- Anthropometry (body measurements e.g. BMI, waist-hip ratio)
- Lung function
- Blood pressure
- Non-fasting Triglycerides, Total cholesterol, and High-density lipoprotein (HDL) cholesterol
- C-reactive protein (hsCRP) (measure of inflammation)
- Cytomegalovirus Optical Density (presence of antibodies against CMV)
They combined the information from all 18 markers to estimate an overall physiological or biological age.
Rather than physiological biomarkers, a related approach is to use performance on basic physical tests. In a previous post, I described a paper that assessed grip strength, and found that "[e]ach 5-kg (11-lb) increment of grip strength below these thresholds was tied to a 20 percent increase for women and a 16 percent increase for men in the risk of death from all causes."
Another study examined the link between physical capability at middle age (age 53) and all-cause mortality over the next 13 years. Physical capability was determined by a combination of three tests: the grip strength test, chair rise time, and standing balance time. The latter was "the longest time, up to a maximum of 30 seconds, participants could maintain a one-legged stance in a standard position with their eyes closed." The researchers found that the bottom 20% performers on the physical tests had a mortality rate 3.68 times that of the top 20% (QH).
Even a ten-second balance test (i.e. standing on one leg for 10 seconds or longer) is correlated with overall mortality (QH).
Ultimately it would be useful to compare the predictions from different methods especially the molecular clock versus phsiological and physical performance measures, and then combine the information from these various biomarkers into a comprehensive estimate.
Figure 1. Aging is correlated with the hypermethylation of CpG islands in the promoters of certain genes. There is also global hypomethylation of cytosine nucleotides throughout the genome during aging (Johnson et al. Rujuvenation Research, 2012).
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